Related Experiment Video

Updated: Jun 26, 2026

Fluorescence Microscopy for ATP Internalization Mediated by Macropinocytosis in Human Tumor Cells and Tumor-xenografted Mice
08:31

Fluorescence Microscopy for ATP Internalization Mediated by Macropinocytosis in Human Tumor Cells and Tumor-xenografted Mice

Published on: June 30, 2021

Human tissue factor pathway inhibitor-2 is internalized by cells and translocated to the nucleus by the importin

Prakasha Kempaiah1, Hitendra S Chand, Walter Kisiel

  • 1Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131-0001, USA.

Archives of Biochemistry and Biophysics
|December 24, 2008
PubMed

Insights

Tissue factor pathway inhibitor-2 (TFPI-2) enters cells and travels to the nucleus, a process crucial for its cancer-fighting apoptosis-inducing function. This nuclear transport is mediated by a specific sequence and the importin system.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Tissue factor pathway inhibitor-2 (TFPI-2) is a serine proteinase inhibitor.
  • TFPI-2 induces caspase-mediated apoptosis in various tumor cells.

Purpose of the Study:

  • To investigate the mechanism of TFPI-2-induced apoptosis.
  • To study the uptake and intracellular trafficking of TFPI-2 in HT-1080 cells.

Main Methods:

  • Cellular uptake and fractionation studies.
  • Immunoprecipitation to identify protein interactions.
  • Analysis of TFPI-2 constructs with deletions.

Main Results:

  • Exogenous TFPI-2 is rapidly internalized and found in both cytosolic and nuclear fractions.
  • Nuclear localization of TFPI-2 requires a Nuclear Localization Sequence (NLS) in its C-terminal tail (residues 191-211).
  • TFPI-2 forms complexes with importin-alpha, indicating importin-mediated nuclear transport.

Conclusions:

  • TFPI-2 is internalized by cells and translocates to the nucleus.
  • The importin system facilitates the nuclear import of TFPI-2.
  • These findings provide initial insights into the cellular mechanisms of TFPI-2 action.

More Related Videos

Delivery of Proteins, Peptides or Cell-impermeable Small Molecules into Live Cells by Incubation with the Endosomolytic Reagent dfTAT10:30

Delivery of Proteins, Peptides or Cell-impermeable Small Molecules into Live Cells by Incubation with the Endosomolytic Reagent dfTAT

Published on: September 2, 2015

Related Concept Videos

Nuclear Localization Signals and Import01:46

Nuclear Localization Signals and Import

Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of  2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Protein Transport to the Inner Chloroplast Membrane01:18

Protein Transport to the Inner Chloroplast Membrane

Proteins targeted to the inner chloroplast membrane, or plastid proteins, are transported by two general pathways: the stop-transfer and the re-insertion or post-import pathways. Most plastid proteins carry N-terminal transit sequences and internal import sequences targeting it to the specific chloroplast subcompartment. Proteins targeted by the stop-transfer pathway have internal hydrophobic sequences that inhibit their translocation into the stroma. As a result, these precursors are arrested...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...